Infection, Human Immunodeficiency VirusPhase 1NCT03234036

A Two-part Study to Compare a Tablet and Capsule Formulation of GSK2838232 With and Without Food, and to Assess the Safety and Drug Levels of Repeated Once-daily Doses of GSK2838232 Without Ritonavir

A Phase 1 study testing GSK2838232 100 mg tablet, GSK2838232 50 mg capsule and Ritonavir 100 mg tablets in people with Infection, Human Immunodeficiency Virus and HIV Infections, run by GlaxoSmithKline at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Infection, Human Immunodeficiency Virus, HIV Infections
What is being tested?: GSK2838232 100 mg tablet, GSK2838232 50 mg capsule and Ritonavir 100 mg tablets
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 26 participants
Where: 1 siteUnited States
Study dates: 2 Aug 2017to 10 Nov 2017
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Between 18 and 55 years of age inclusive, at the time of signing the informed consent.
Healthy as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, and outside the reference range for the population being studied, may be included only if the Investigator in consultation with the medical monitor, if required, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
A creatinine clearance (CLcr) > 80 milliliter per minute (mL/min) as determined by Cockcroft-Gault equation: CLcr = (140 minus age) multiplied by weight divided by (72 multiplied by serum creatinine) (times 0.85 if female) where age is in years, weight in kilogram (kg), and serum creatinine is in units of milligram per deciliter (mg/dL).
Body weight >=50.0 kg (110 pounds [lbs.]) for men and >=45.0 kg (99 lbs) for women and body mass index (BMI) within the range 18.5 to 31.0 kg/meter (m)^2 (inclusive).
Males or females.

Show all 16Show fewer

A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin [hCG] test), not lactating, and of non-reproductive potential which is defined as:
Reproductive potential:
There is no definitive drug-drug interaction (DDI) information with GSK2838232 and an interaction with oral contraceptives is possible, so other (barrier, inter-uterine device etc.) methods of contraception will be required. Females of reproductive potential may only be enrolled if they are using two forms of complementary contraception, which must include at least one barrier method. They will be counseled on safer sex practices. Fertile females, who have an established, long-term lifestyle of sexual abstinence, or only same sex partners, require no other means of birth control.
Non-reproductive potential:
Pre-menopausal females with one of the following: Documented tubal ligation; documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; hysterectomy; documented Bilateral Oophorectomy.
Postmenopausal defined as 12 months of spontaneous amenorrhea in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause. Females on hormone replacement therapy (HRT) must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until one week after the last dose of study medication.
Vasectomy with documentation of azoospermia.
Male condom plus partner use of one of the contraceptive options below: Contraceptive subdermal implant with a <1 percent rate of failure per year; intrauterine device or intrauterine system with a <1 percent rate of failure per year; oral contraceptive, either combined or progestogen alone or injectable progestogen; contraceptive vaginal ring; percutaneous contraceptive patches.
Capable of giving signed informed consent.

Who cannot join

ALT >1.5 times upper limit of normal (ULN)
Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent).
Current or chronic history of liver disease, or known hepatic or biliary abnormalities.
Subjects who have asthma or a history of asthma.
Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.
Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GlaxoSmithKline medical monitor, the medication will not interfere with the study procedures or compromise participant safety.

Show all 35Show fewer

History of regular alcohol consumption (within 6 months prior to screening or unable to refrain from alcohol use from 5 days prior to admission through the last blood sample collected) defined as:
For United States sites: an average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 gram of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
Regular use of tobacco- or nicotine- containing products within 6 months prior to screening. Unable to refrain from smoking from the Screening Visit through the last blood sample collected. As confirmed by a urine cotinine test.
History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.
Presence of hepatitis B surface antigen (HBsAg), or positive hepatitis C virus (HCV) test result at screening or within 3 months prior to first dose of study treatment.
Screening or Baseline cardiac troponin I greater than the 99 percent cutoff (>0.045 nanogram [ng]/mL by the Dimension Vista cTnI assay) for a given assay.
A positive pre-study drug/alcohol screen.
A positive test for human immunodeficiency virus (HIV) antibody.
Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 56 days.
The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
Any symptomatic arrhythmia (except isolated extra systoles).
Sustained cardiac arrhythmias (such as atrial fibrillation or flutter, supraventricular tachycardia (>= 10 consecutive beats), complete heart block).
Non-sustained or sustained ventricular tachycardia (defined as >=3 consecutive ventricular ectopic beats).
Any conduction abnormality (including but not specific to left or right incomplete or complete bundle branch block, atrioventricular (AV) block [2nd degree or higher], Wolff Parkinson White (WPW) syndrome etc.).
Sinus Pauses >3 seconds.
300 or more supraventricular ectopic beats in 24 hours.
250 or more ventricular ectopic beats in 24 hours.
Any clinically significant abnormal echocardiogram finding.
Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination):
Heart rate <45 or >100 beats per minute (bpm) for males; <50 or >100 bpm for females
PR interval <120 or >220 milliseconds (msec)
QRS duration <70 or >120 msec
QTc interval (Fridericia's) >450 msec
Evidence of previous myocardial infarction (does not include ST segment changes associated with re-polarization).
Any conduction abnormality (including but not specific to left or right complete bundle branch block, AV block [2nd degree or higher], WPW syndrome).
Sinus Pauses >3 seconds.
Any significant arrhythmia which, in the opinion of the Investigator or GSK medical monitor, will interfere with the safety for the individual subject.
Non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular ectopic beats).

Trial locations and contacts

1 site in 1 country.

United States1 site

GSK Investigational Site
Baltimore, Maryland, 21225

Other trials in United States

About this study

Official title: A Two Part Study to Assess i) the Relative Bioavailability and Food Effect of a Novel Tablet Formulation of Boosted-GSK2838232 Compared to Capsule and ii) the Safety and Pharmacokinetics of Repeated Once-Daily Doses of Non-boosted GSK2838232

This study will be conducted in two Parts to confirm the acceptability/selection of a tablet formulation for future clinical development of GSK2838232. Part 1 of the study will assess single ritonavir (RTV)-boosted doses of a new tablet formulation given with food (containing approximately 30% fat) against the reference capsule formulation also given with food and then will assess the impact of fasted conditions on the tablet performance. In Part 2, non-boosted GSK2838232 will be given as once-daily tablet doses for 11 days in a separate group of subjects, assuming the tablet performance is considered acceptable from Part 1. Approximately 16 healthy subjects will be enrolled to provide at least 12 evaluable subjects through the three study periods in Part 1. 10 healthy subjects will be enrolled to provide at least 8 evaluable subjects through the single study period in Part 2. The maximum duration of study participation will be approximately 9 to 10 weeks for Part 1; and 8 to 9 weeks for Part 2.

Conditions: Infection, Human Immunodeficiency Virus, HIV Infections
Being tested: GSK2838232 100 mg tablet, GSK2838232 50 mg capsule, Ritonavir 100 mg tablets, Placebo for GSK2838232 tablets
Keywords: GSK2838232, safety, food effect, capsule, healthy, PK, tablet
Medical subject headings: Infections, Acquired Immunodeficiency Syndrome, HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GSK2838232 100 mg tabletDrug
It is a white to slightly colored tablet. It will be supplied as prefilled tablets in bulk for dispensing to subjects at the site according to the treatment code.
GSK2838232 50 mg capsuleDrug
It is a pink unmarked capsule. It will be supplied as prefilled capsules in bulk for dispensing to subjects at the site according to the treatment code.
Ritonavir 100 mg tabletsDrug
It is a white film-coated ovaloid tablets.
Placebo for GSK2838232 tabletsDrug
It is a white to slightly colored tablet. The placebo tablets supplied will not be identical to GSK2838232 tablets. It will be administered by site staff via an opaque card or paper tube.

Study groups in NCT03234036
Study group	Role	What they receive
Treatment sequence ABC: Part 1	Experimental	A single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation will be administered under fed conditions (treatment A) in period 1 in Part 1A. A single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation will be administered under fed conditions (treatment B) in period 2 in Part 1A. Both these treatments in Part 1A will be administered with RTV in fed state with a washout of 10 days. A single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation (with RTV) will be administered under fasted conditions (treatment C) in period 3 in Part 1B. There will be a wash out of 15 days between Part 1A and Part 1B. Receives: Drug: GSK2838232 100 mg tablet; Drug: GSK2838232 50 mg capsule; Drug: Ritonavir 100 mg tablets
Treatment sequence BAC: Part 1	Experimental	A single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation will be administered under fed conditions (treatment B) in period 1 in Part 1A. A single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation will be administered under fed conditions (treatment A) in period 2 in Part 1A. A single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation (with RTV) will be administered under fasted conditions (treatment C) in period 3 in Part 1B. There will be a wash out of 15 days between Part 1A and Part 1B. Receives: Drug: GSK2838232 100 mg tablet; Drug: GSK2838232 50 mg capsule; Drug: Ritonavir 100 mg tablets
GSK2838232 tablet without RTV: Part 2	Experimental	In Part 2, subjects will receive non-RTV boosted GSK2838232 500 mg, given as single daily doses for 11 days. The dose will not exceed 500 mg (as 5 x 100 mg tablets) once daily (QD). Receives: Drug: GSK2838232 100 mg tablet
Placebo without RTV: Part 2	Placebo comparator	In Part 2, subjects will receive a Placebo given as single daily doses for 11 days. Receives: Drug: Placebo for GSK2838232 tablets

What is being measured

The primary outcome is the main question the study is designed to answer.

Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as tablet and capsule formulation in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods. Pharmacokinetic Population comprised of all participants in the Safety Population who had at least 1 non-missing pharmacokinetic assessment (Non-quantifiable [NQ] values were considered as non-missing values).
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1 and 2 of Part 1
Part 1: Maximum Observed Concentration (Cmax) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as tablet and capsule formulation in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1 and 2 of Part 1
Part 1: AUC (0-infinity) Following Administration of GSK2838232 Tablet in Fasted and Fed State
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as tablet formulation in fed and fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1
Part 1: Cmax Following Administration of GSK2838232 Tablet in Fasted and Fed State
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as tablet formulation in fed and fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1
Part 1: Time of Occurrence of Cmax (Tmax) Following Administration of GSK2838232 Tablet in Fasted and Fed State
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as tablet formulation in fed and fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1
Part 2: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/ birth defect, is associated with liver injury or impaired liver function or any other situations as per medical or scientific judgment. Safety Population comprised of all participants who received at least 1 dose of the study treatment (including placebo) with at least 1 post-Baseline safety assessment. Number of participants with SAEs and common non-SAEs (>=5%) are presented.
Measured: Up to 25 days
Part 2: Number of Participants With Worst Case Hematology Results to Potential Clinical Importance (PCI) Criteria
Blood samples were collected from participants for analysis of following hematology parameters; hematocrit, hemoglobin, leukocytes, lymphocytes, neutrophils and platelets. PCI ranges were < 0.075 or >0.54 proportion of red blood cells in blood for hematocrit, <25 or >180 grams per liter (g/L) for hemoglobin, < 3 or >20 cells per liter (cells/L) for leukocytes, 0.8 x10^9 cells/L for lymphocytes, 1.5 x10^9 cells/L for neutrophils, and <100 or >550 cells/L for platelets. Participants were counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (example given [e.g.], High to High), or whose value became within range, were recorded in the "To within Range or No Change" category.
Measured: Up to 25 days
Part 2: Number of Participants With Worst Case Clinical Chemistry Results to PCI Criteria
Blood samples were collected from participants for analysis of following clinical chemistry parameters; glucose, alanine aminotransferase (ALT), albumin, alkaline phosphatase, aspartate aminotransferase (AST), bilirubin, calcium, potassium and sodium. PCI ranges were <30 g/L for albumin, <2 or >2.75 millimoles per liter (mmol/L) for calcium, <3 or >9 mmol/L for glucose, >=2 times Upper limit of Normal (ULN) units per liter (U/L) for ALT, >=2 times ULN U/L for alkaline phosphatase, >=2 times ULN U/L for AST, >=1.5 times ULN micromoles per liter (µmol/L) for bilirubin, <3 or >5.5 mmol/L for potassium, and <130 or >150 mmol/L for sodium. Participants were counted in the worst case category that their value changes to (low, within range or no change,or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "To within Range or No Change" category.
Measured: Up to 25 days
Part 2: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Criteria
Urine samples were collected from participants for analysis of following urinalysis parameters; specific gravity, potential of hydrogen (pH), presence of glucose, protein, occult blood, ketones in urine analyzed by dipstick method. The dipstick test gives results in a semi-quantitative manner. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The reference range is 1.002-1.030. Urine pH is an acid-base measurement. Normal urine has a slightly acid pH (5.0 - 6.0). Participants were counted in the worst case category that their value changes to (low, normal or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the "To Normal or No Change" category.
Measured: Up to 25 days
Part 2: Blood Pressure at Indicated Time Points
Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured in supine position after 10 minutes rest for the participants at indicated time points.
Measured: Day -1; Pre-dose, 1, 4 hours on Day 1; 24 hours (Day 2); 48 hours (Day 3); 72 hours (Day 4), Days 5, 6, 7, 8, 9, 10; Pre-dose, 1, 4 , 24, 48, 72 hours on Day 11; Follow-up (Day 25)
Part 2: Change From Baseline in Blood Pressure
SBP and DBP were measured in supine position after 10 minutes rest for participants at indicated time points. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Measured: Baseline (Day -1) and 1, 4 hours on Day 1; 24 hours (Day 2); 48 hours (Day 3); 72 hours (Day 4), Days 5, 6, 7, 8, 9, 10; Pre-dose, 1, 4 , 24, 48, 72 hours on Day 11; Follow-up (Day 25)
Part 2: Pulse Rate at Indicated Time Points
Pulse rate of participants was measured in supine position after 10 minutes rest at indicated time points.
Measured: Day -1; Pre-dose, 1, 4 hours on Day 1; 24 hours (Day 2); 48 hours (Day 3); 72 hours (Day 4), Days 5, 6, 7, 8, 9, 10; Pre-dose, 1, 4 , 24, 48, 72 hours on Day 11; Follow-up (Day 25)
Part 2: Change From Baseline in Pulse Rate
Pulse rate was measured in supine position after 10 minutes rest at indicated time points. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Measured: Baseline (Day -1) and 1, 4 hours on Day 1; 24 hours (Day 2); 48 hours (Day 3); 72 hours (Day 4), Days 5, 6, 7, 8, 9, 10; Pre-dose, 1, 4 , 24, 48, 72 hours on Day 11; Follow-up (Day 25)
Part 2: Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings have been presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Measured: Day -1; 1, 4, 12 hours on Day 1; Days 2, 3, 5, 8; 1, 4, 12, 24 Hours on Day 11; Follow-up (Day 25)
Part 2: Change From Baseline in Mean Heart Rate Values as ECG Parameter
Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates the heart rate. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Measured: Baseline (Day -1) and 1, 4, 12 hours on Day 1; Days 2, 3 5, 8; Pre-dose, 1, 4, 12, 24 hours Day 11; Follow-up (Day 25)
Part 2: Change From Baseline in PR Interval, QRS, QT Interval, and QTcF Interval as ECG Parameters
Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates measures PR, QRS, QT and QTcF intervals. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Measured: Baseline (Day -1) and 1, 4, 12 hours on Day 1; Days 2, 3 5, 8; Pre-dose, 1, 4, 12, 24 hours Day 11; Follow-up (Day 25)
Part 2: Area Under the Plasma Drug Concentration Time Curve From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2
Part 2: Cmax Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2
Part 2: Observed Concentration at the End of the Dosing Interval (Ctau) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2
Part 2: Tmax Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2
Part 2: Lag-time (Tlag) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 1
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Tlag is a time delay between drug administration and first observed concentration. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1 in Part 2
Part 2: AUC(0-infinity) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 11
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2
Part 2: Apparent Terminal Phase Half-life (T1/2) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 11
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2
Part 2: Time of Last Quantifiable Concentration (Tlast) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 11
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2

Secondary outcomes (21)

Part 1: Number of Participants With SAEs and Non-SAEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/ birth defect, is associated with liver injury or impaired liver function or any other situations as per medical or scientific judgment. Number of participants with SAEs and common non-SAEs (>=5%) are presented.
Measured: Up to 60 days
Part 1: Number of Participants With Worst Case Hematology Results to PCI Criteria
Blood samples were collected from participants for analysis of following hematology parameters; hematocrit, hemoglobin, leukocytes, lymphocytes, neutrophils and platelets. PCI ranges were >0.54 as proportion of red blood cells in blood for hematocrit, >180 g/L for hemoglobin, < 3 or >20 cells/L for leukocytes, 0.8 x10^9 cells/L for lymphocytes, 1.5 x10^9 cells/L for neutrophils, and <100 or >550 cells/L for platelets. Participants were counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "To within Range or No Change" category.
Measured: Up to 60 days
Part 1: Number of Participants With Worst Case Clinical Chemistry Results to PCI Criteria
Blood samples were collected from participants for analysis of following clinical chemistry parameters; glucose, ALT, albumin, alkaline phosphatase, AST, bilirubin, calcium, potassium and sodium. PCI ranges were <30 g/L for albumin, <2 or 2.75 mmol/L for calcium, <3 or >9 mmol/L for glucose, >=2 times ULN U/L for ALT, >=2 times ULN U/L for alkaline phosphatase, >=2 times ULN U/L for AST, >=1.5 times ULN µmol/L for bilirubin, <3 or >5.5 mmol/L for potassium, and <130 or >150 mmol/L for sodium. Participants were counted in the worst case category that their value changes to (low, within range or no change,or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "To within Range or No Change" category.
Measured: Up to 60 days
Part 1: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Criteria
Urine samples were collected from participants for analysis of following urinalysis parameters; specific gravity, pH, presence of glucose, protein, occult blood, ketones in urine analyzed by dipstick method. The dipstick test gives results in a semi-quantitative manner. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The reference range is 1.002-1.030. Urine pH is an acid-base measurement. Normal urine has a slightly acid pH (5.0 - 6.0). Participants were counted in the worst case category that their value changes to (low, normal or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the "To Normal or No Change" category.
Measured: Up to 60 days
Part 1: Blood Pressure at Indicated Time Points
SBP and DBP of participants were measured in supine position after 10 minutes rest at indicated time points.
Measured: Day -2; Day -1; Pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72 Hours on Day 1
Part 1: Change From Baseline in Blood Pressure
SBP and DBP were measured in supine position after 10 minutes rest for the participant at indicated time points. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Measured: Baseline (Day -1) and 1, 2, 4, 6, 8, 12, 24, 48, 72 Hours on Day 1
Part 1: Pulse Rate at Indicated Time Points
Pulse rate was measured in supine position after 10 minutes rest for the participant at indicated time points.
Measured: Day -2; Day -1; Pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72 Hours on Day 1
Part 1: Change From Baseline in Pulse Rate
Pulse rate was measured in supine position after 10 minutes rest for the participant at indicated time points. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Measured: Baseline (Day -1) and 1, 2, 4, 6, 8, 12, 24, 48, 72 Hours on Day 1
Part 1: Number of Participants With Abnormal ECG Findings
Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QTcF intervals. CS and NCS abnormal ECG findings have been presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Measured: Day -2, Day -1; 1, 2, 4, 6, 8, , 12, 24, 48, 72 hours on Day 1
Part 1: Change From Baseline in Mean Heart Rate Values as ECG Parameter
Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates the heart rate. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Measured: Baseline (Day -1) and 1, 2, 4, 6, 8, 12, 24, 48, 72 hours on Day 1
Part 1: Change From Baseline in PR Interval, QRS, QT Interval, and QTcF Interval as ECG Parameters
Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates measures PR, QRS, QT and QTcF intervals. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Measured: Baseline (Day -1) and 1, 2, 4, 6, 8, 12, 24, 48, 72 hours on Day 1
Part 1: Tlag Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Tlag is a time delay between drug administration and first observed concentration. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1
Part 1: Tmax Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1
Part 1: T1/2 Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1
Part 1: Tlast Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1
Part 1: Plasma Drug Concentration at 24 Hours (C24) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1
Part 1: AUC(0-t) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1
Part 2: Slope of Pre-dose Concentration of GSK2838232 Administered as Non-boosted Once-daily Doses of a Tablet Formulation to Assess Achievement of Steady State
Blood sample were collected at indicated time points to assess pre-dose concentration of GSK2838232 when administered as non-boosted once-daily doses of a tablet formulation for 11 days in Part 2. Slope and 90 percent confidence interval have been presented.
Measured: Pre-dose on Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10 and Day 11 in Part 2
Part 2: Accumulation Ratio Calculated From AUC(0-tau) Following Administration of GSK2838232 as Non-boosted Once-daily Doses of a Tablet Formulation
Blood sample were collected at indicated time points to calculate accumulation ratio from AUC(0-tau) following administration of GSK2838232 as non-boosted once-daily doses of a tablet formulation. Accumulation ratio of GSK2838232 was evaluated by Day 11, AUC (0-tau) divided by Day 1, AUC (0-tau).
Measured: Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2
Part 2: Accumulation Ratio Calculated From Cmax Following Administration of GSK2838232 as Non-boosted Once-daily Doses of a Tablet Formulation
Blood sample were collected at indicated time points to calculate accumulation ratio from Cmax following administration of GSK2838232 as non-boosted once-daily doses of a tablet formulation. Accumulation ratio of GSK2838232 was evaluated by Day 11, Cmax divided by Day 1, Cmax.
Measured: Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2
Part 2: Accumulation Ratio Calculated From Ctau Following Administration of GSK2838232 as Non-boosted Once-daily Doses of a Tablet Formulation
Blood sample were collected at indicated time points to calculate accumulation ratio from Ctau following administration of GSK2838232 as non-boosted once-daily doses of a tablet formulation. Accumulation ratio of GSK2838232 was evaluated by Day 11, Ctau divided by Day 1, Ctau.
Measured: Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

2 Aug 201710 Nov 2017

First posted31 Jul 2017
Study start2 Aug 2017
Primary completion10 Nov 2017
Study completion10 Nov 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Infection, Human Immunodeficiency VirusStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Model description: The randomization number will determine the allocation of treatment sequences (ABC or BAC) for Part 1, and of treatment (GSK2838232 without RTV or placebo) for Part 2. Allocation to treatment for Part 1A or Part 1B (with Part 2 being fixed) will be according to a predetermined random order.
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 26 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03234036
Sponsor's protocol ID: 205820
Status last verified: Oct 2020
First submitted: 26 Jul 2017
Last updated: 28 Oct 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: IPD for this study is available via the Clinical Study Data Request site.

Publications

Johnson M, Jewell RC, Gan J, Dumont E, Burns O, Johns BA. A Phase 1 Study to Assess the Relative Bioavailability, Food Effect, and Safety of a Tablet Formulation of GSK2838232, a Novel HIV Maturation Inhibitor in Healthy Participants After Single and Repeated Doses. Clin Pharmacol Drug Dev. 2020 Nov;9(8):972-977. doi: 10.1002/cpdd.820. Epub 2020 Jun 18.
PubMed 32558338

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruiting
Bwelela Easy Study
HIV, HIV - Human Immunodeficiency Virus
RecruitingPhase 2
Doravirine (DOR) in Human Immunodeficiency Virus (HIV)-Infected Children Aged 4 Weeks to <12 Years and <45 kg (MK-1439-066)
Human Immunodeficiency Virus (HIV) Infection
RecruitingPhase 1
Dasatinib for HIV-1 Reservoir Reduction
HIV Infections
RecruitingObservational study
Leukapheresis to Obtain Plasma or Lymphocytes for Studies of HIV-infected Patients, Including Long-term Non-progressors
HIV
RecruitingObservational study
Evaluation of Patients With HAM/TSP
HTLV-I Infection, Tropical Spastic Paraparesis

All Infection, Human Immunodeficiency Virus trials

Study at a glance

From the registry record, last updated by the sponsor on 28 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Two Part Study to Assess i) the Relative Bioavailability and Food Effect of a Novel Tablet Formulation of Boosted-GSK2838232 Compared to Capsule and ii) the Safety and Pharmacokinetics of Repeated Once-Daily Doses of Non-boosted GSK2838232
ClinicalTrials.gov ID: NCT03234036
Acronym / sponsor ID: 205820
Conditions: Infection, Human Immunodeficiency Virus, HIV Infections
Keywords: GSK2838232, safety, food effect, capsule, healthy, PK, tablet
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 26 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 2 Aug 2017 (actual)
Primary completion: 10 Nov 2017 (actual)
Study completion: 10 Nov 2017 (actual)
First posted: 31 Jul 2017 (actual)
Results: Posted 7 Mar 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 4
Model description: The randomization number will determine the allocation of treatment sequences (ABC or BAC) for Part 1, and of treatment (GSK2838232 without RTV or placebo) for Part 2. Allocation to treatment for Part 1A or Part 1B (with Part 2 being fixed) will be according to a predetermined random order.

Arm	Type	Receives
Treatment sequence ABC: Part 1	Experimental	Drug: GSK2838232 100 mg tablet, Drug: GSK2838232 50 mg capsule, Drug: Ritonavir 100 mg tabletsA single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation will be administered under fed conditions (treatment A) in period 1 in Part 1A. A single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation will be administered under fed conditions (treatment B) in period 2 in Part 1A. Both these treatments in Part 1A will be administered with RTV in fed state with a washout of 10 days. A single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation (with RTV) will be administered under fasted conditions (treatment C) in period 3 in Part 1B. There will be a wash out of 15 days between Part 1A and Part 1B.
Treatment sequence BAC: Part 1	Experimental	Drug: GSK2838232 100 mg tablet, Drug: GSK2838232 50 mg capsule, Drug: Ritonavir 100 mg tabletsA single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation will be administered under fed conditions (treatment B) in period 1 in Part 1A. A single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation will be administered under fed conditions (treatment A) in period 2 in Part 1A. A single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation (with RTV) will be administered under fasted conditions (treatment C) in period 3 in Part 1B. There will be a wash out of 15 days between Part 1A and Part 1B.
GSK2838232 tablet without RTV: Part 2	Experimental	Drug: GSK2838232 100 mg tabletIn Part 2, subjects will receive non-RTV boosted GSK2838232 500 mg, given as single daily doses for 11 days. The dose will not exceed 500 mg (as 5 x 100 mg tablets) once daily (QD).
Placebo without RTV: Part 2	Placebo comparator	Drug: Placebo for GSK2838232 tabletsIn Part 2, subjects will receive a Placebo given as single daily doses for 11 days.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (16 listed)

Between 18 and 55 years of age inclusive, at the time of signing the informed consent.
Healthy as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, and outside the reference range for the population being studied, may be included only if the Investigator in consultation with the medical monitor, if required, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
A creatinine clearance (CLcr) > 80 milliliter per minute (mL/min) as determined by Cockcroft-Gault equation: CLcr = (140 minus age) multiplied by weight divided by (72 multiplied by serum creatinine) (times 0.85 if female) where age is in years, weight in kilogram (kg), and serum creatinine is in units of milligram per deciliter (mg/dL).
Body weight >=50.0 kg (110 pounds [lbs.]) for men and >=45.0 kg (99 lbs) for women and body mass index (BMI) within the range 18.5 to 31.0 kg/meter (m)^2 (inclusive).

Key exclusion criteria (35 listed)

ALT >1.5 times upper limit of normal (ULN)
Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent).
Current or chronic history of liver disease, or known hepatic or biliary abnormalities.
Subjects who have asthma or a history of asthma.
Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GSK2838232 100 mg tabletIt is a white to slightly colored tablet. It will be supplied as prefilled tablets in bulk for dispensing to subjects at the site according to the treatment code.	Drug	GSK2838232 tablet without RTV: Part 2, Treatment sequence ABC: Part 1, Treatment sequence BAC: Part 1
GSK2838232 50 mg capsuleIt is a pink unmarked capsule. It will be supplied as prefilled capsules in bulk for dispensing to subjects at the site according to the treatment code.	Drug	Treatment sequence ABC: Part 1, Treatment sequence BAC: Part 1
Ritonavir 100 mg tabletsIt is a white film-coated ovaloid tablets.	Drug	Treatment sequence ABC: Part 1, Treatment sequence BAC: Part 1
Placebo for GSK2838232 tabletsIt is a white to slightly colored tablet. The placebo tablets supplied will not be identical to GSK2838232 tablets. It will be administered by site staff via an opaque card or paper tube.	Drug	Placebo without RTV: Part 2

Primary outcome

Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1 and 2 of Part 1
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as tablet and capsule formulation in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods. Pharmacokinetic Population comprised of all participants in the Safety Population who had at least 1 non-missing pharmacokinetic assessment (Non-quantifiable [NQ] values were considered as non-missing values).
Part 1: Maximum Observed Concentration (Cmax) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1 and 2 of Part 1
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as tablet and capsule formulation in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 1: AUC (0-infinity) Following Administration of GSK2838232 Tablet in Fasted and Fed State
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as tablet formulation in fed and fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 1: Cmax Following Administration of GSK2838232 Tablet in Fasted and Fed State
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as tablet formulation in fed and fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 1: Time of Occurrence of Cmax (Tmax) Following Administration of GSK2838232 Tablet in Fasted and Fed State
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as tablet formulation in fed and fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs
Time frame: Up to 25 days
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/ birth defect, is associated with liver injury or impaired liver function or any other situations as per medical or scientific judgment. Safety Population comprised of all participants who received at least 1 dose of the study treatment (including placebo) with at least 1 post-Baseline safety assessment. Number of participants with SAEs and common non-SAEs (>=5%) are presented.
Part 2: Number of Participants With Worst Case Hematology Results to Potential Clinical Importance (PCI) Criteria
Time frame: Up to 25 days
Blood samples were collected from participants for analysis of following hematology parameters; hematocrit, hemoglobin, leukocytes, lymphocytes, neutrophils and platelets. PCI ranges were < 0.075 or >0.54 proportion of red blood cells in blood for hematocrit, <25 or >180 grams per liter (g/L) for hemoglobin, < 3 or >20 cells per liter (cells/L) for leukocytes, 0.8 x10^9 cells/L for lymphocytes, 1.5 x10^9 cells/L for neutrophils, and <100 or >550 cells/L for platelets. Participants were counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (example given [e.g.], High to High), or whose value became within range, were recorded in the "To within Range or No Change" category.
Part 2: Number of Participants With Worst Case Clinical Chemistry Results to PCI Criteria
Time frame: Up to 25 days
Blood samples were collected from participants for analysis of following clinical chemistry parameters; glucose, alanine aminotransferase (ALT), albumin, alkaline phosphatase, aspartate aminotransferase (AST), bilirubin, calcium, potassium and sodium. PCI ranges were <30 g/L for albumin, <2 or >2.75 millimoles per liter (mmol/L) for calcium, <3 or >9 mmol/L for glucose, >=2 times Upper limit of Normal (ULN) units per liter (U/L) for ALT, >=2 times ULN U/L for alkaline phosphatase, >=2 times ULN U/L for AST, >=1.5 times ULN micromoles per liter (µmol/L) for bilirubin, <3 or >5.5 mmol/L for potassium, and <130 or >150 mmol/L for sodium. Participants were counted in the worst case category that their value changes to (low, within range or no change,or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "To within Range or No Change" category.
Part 2: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Criteria
Time frame: Up to 25 days
Urine samples were collected from participants for analysis of following urinalysis parameters; specific gravity, potential of hydrogen (pH), presence of glucose, protein, occult blood, ketones in urine analyzed by dipstick method. The dipstick test gives results in a semi-quantitative manner. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The reference range is 1.002-1.030. Urine pH is an acid-base measurement. Normal urine has a slightly acid pH (5.0 - 6.0). Participants were counted in the worst case category that their value changes to (low, normal or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the "To Normal or No Change" category.
Part 2: Blood Pressure at Indicated Time Points
Time frame: Day -1; Pre-dose, 1, 4 hours on Day 1; 24 hours (Day 2); 48 hours (Day 3); 72 hours (Day 4), Days 5, 6, 7, 8, 9, 10; Pre-dose, 1, 4 , 24, 48, 72 hours on Day 11; Follow-up (Day 25)
Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured in supine position after 10 minutes rest for the participants at indicated time points.
Part 2: Change From Baseline in Blood Pressure
Time frame: Baseline (Day -1) and 1, 4 hours on Day 1; 24 hours (Day 2); 48 hours (Day 3); 72 hours (Day 4), Days 5, 6, 7, 8, 9, 10; Pre-dose, 1, 4 , 24, 48, 72 hours on Day 11; Follow-up (Day 25)
SBP and DBP were measured in supine position after 10 minutes rest for participants at indicated time points. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Part 2: Pulse Rate at Indicated Time Points
Time frame: Day -1; Pre-dose, 1, 4 hours on Day 1; 24 hours (Day 2); 48 hours (Day 3); 72 hours (Day 4), Days 5, 6, 7, 8, 9, 10; Pre-dose, 1, 4 , 24, 48, 72 hours on Day 11; Follow-up (Day 25)
Pulse rate of participants was measured in supine position after 10 minutes rest at indicated time points.
Part 2: Change From Baseline in Pulse Rate
Time frame: Baseline (Day -1) and 1, 4 hours on Day 1; 24 hours (Day 2); 48 hours (Day 3); 72 hours (Day 4), Days 5, 6, 7, 8, 9, 10; Pre-dose, 1, 4 , 24, 48, 72 hours on Day 11; Follow-up (Day 25)
Pulse rate was measured in supine position after 10 minutes rest at indicated time points. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Part 2: Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Time frame: Day -1; 1, 4, 12 hours on Day 1; Days 2, 3, 5, 8; 1, 4, 12, 24 Hours on Day 11; Follow-up (Day 25)
Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings have been presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Part 2: Change From Baseline in Mean Heart Rate Values as ECG Parameter
Time frame: Baseline (Day -1) and 1, 4, 12 hours on Day 1; Days 2, 3 5, 8; Pre-dose, 1, 4, 12, 24 hours Day 11; Follow-up (Day 25)
Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates the heart rate. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Part 2: Change From Baseline in PR Interval, QRS, QT Interval, and QTcF Interval as ECG Parameters
Time frame: Baseline (Day -1) and 1, 4, 12 hours on Day 1; Days 2, 3 5, 8; Pre-dose, 1, 4, 12, 24 hours Day 11; Follow-up (Day 25)
Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates measures PR, QRS, QT and QTcF intervals. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Part 2: Area Under the Plasma Drug Concentration Time Curve From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State
Time frame: Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: Cmax Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State
Time frame: Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: Observed Concentration at the End of the Dosing Interval (Ctau) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State
Time frame: Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: Tmax Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State
Time frame: Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: Lag-time (Tlag) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 1
Time frame: Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1 in Part 2
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Tlag is a time delay between drug administration and first observed concentration. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: AUC(0-infinity) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 11
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: Apparent Terminal Phase Half-life (T1/2) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 11
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: Time of Last Quantifiable Concentration (Tlast) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 11
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.

21 secondary outcomes

Part 1: Number of Participants With SAEs and Non-SAEs
Time frame: Up to 60 days
Part 1: Number of Participants With Worst Case Hematology Results to PCI Criteria
Time frame: Up to 60 days
Part 1: Number of Participants With Worst Case Clinical Chemistry Results to PCI Criteria
Time frame: Up to 60 days
Part 1: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Criteria
Time frame: Up to 60 days
Part 1: Blood Pressure at Indicated Time Points
Time frame: Day -2; Day -1; Pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72 Hours on Day 1
Part 1: Change From Baseline in Blood Pressure
Time frame: Baseline (Day -1) and 1, 2, 4, 6, 8, 12, 24, 48, 72 Hours on Day 1
Part 1: Pulse Rate at Indicated Time Points
Time frame: Day -2; Day -1; Pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72 Hours on Day 1
Part 1: Change From Baseline in Pulse Rate
Time frame: Baseline (Day -1) and 1, 2, 4, 6, 8, 12, 24, 48, 72 Hours on Day 1
Part 1: Number of Participants With Abnormal ECG Findings
Time frame: Day -2, Day -1; 1, 2, 4, 6, 8, , 12, 24, 48, 72 hours on Day 1
Part 1: Change From Baseline in Mean Heart Rate Values as ECG Parameter
Time frame: Baseline (Day -1) and 1, 2, 4, 6, 8, 12, 24, 48, 72 hours on Day 1
Part 1: Change From Baseline in PR Interval, QRS, QT Interval, and QTcF Interval as ECG Parameters
Time frame: Baseline (Day -1) and 1, 2, 4, 6, 8, 12, 24, 48, 72 hours on Day 1
Part 1: Tlag Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1
Part 1: Tmax Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1
Part 1: T1/2 Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1
Part 1: Tlast Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1
Part 1: Plasma Drug Concentration at 24 Hours (C24) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1
Part 1: AUC(0-t) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1
Part 2: Slope of Pre-dose Concentration of GSK2838232 Administered as Non-boosted Once-daily Doses of a Tablet Formulation to Assess Achievement of Steady State
Time frame: Pre-dose on Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10 and Day 11 in Part 2
Part 2: Accumulation Ratio Calculated From AUC(0-tau) Following Administration of GSK2838232 as Non-boosted Once-daily Doses of a Tablet Formulation
Time frame: Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2
Part 2: Accumulation Ratio Calculated From Cmax Following Administration of GSK2838232 as Non-boosted Once-daily Doses of a Tablet Formulation
Time frame: Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2
Part 2: Accumulation Ratio Calculated From Ctau Following Administration of GSK2838232 as Non-boosted Once-daily Doses of a Tablet Formulation
Time frame: Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2

Results and safety

Results posted to the registry on 7 Mar 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
GSK2838232 Capsule Fed/Tablet Fed/Tablet Fasted With Ritonavir	8	8
GSK2838232 Tablet Fed/Capsule Fed/Tablet Fasted With Ritonavir	8	8
Part 2: Placebo	0	0
Part 2: GSK2838232 500 mg Tablet Fed	0	0

Primary outcome: Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State

Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1 and 2 of Part 1. Geometric mean (Geometric Coefficient of Variation). Unit: Hours*nanogram per milliliter

Measure	Part 1: GSK2838232 200 mg/Ritonavir Capsule Fed n = 15	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed n = 15
Value	4672.28 (40.68)	4437.98 (30.83)

Population analysed: Pharmacokinetic Population

Primary outcome: Part 1: Maximum Observed Concentration (Cmax) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State

Measure	Part 1: GSK2838232 200 mg/Ritonavir Capsule Fed n = 15	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed n = 15
Value	109.054 (48.01)	118.118 (27.59)

Population analysed: Pharmacokinetic Population

Primary outcome: Part 1: AUC (0-infinity) Following Administration of GSK2838232 Tablet in Fasted and Fed State

Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1. Geometric mean (Geometric Coefficient of Variation). Unit: Hours*nanogram per milliliter

Measure	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed n = 15	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fasted n = 14
Value	4437.98 (30.83)	1816.27 (36.42)

Population analysed: Pharmacokinetic Population

Primary outcome: Part 1: Cmax Following Administration of GSK2838232 Tablet in Fasted and Fed State

Measure	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed n = 15	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fasted n = 14
Value	118.118 (27.59)	50.437 (35.61)

Population analysed: Pharmacokinetic Population

21 secondary outcomes are reported in the full results.

Adverse events

Time frame: Serious adverse events (SAEs) and Non-SAEs were collected up to 60 days in Part 1 of the study and up to 25 days in Part 2 of the study.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part 1: GSK2838232 200 mg/Ritonavir Capsule Fed	0 of 15 (0%)	3 of 15 (20%)	0 of 15
Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed	0 of 15 (0%)	2 of 15 (13.3%)	0 of 15
Part 1: GSK 200 mg/Ritonavir Tablet Fasted	0 of 14 (0%)	1 of 14 (7.1%)	0 of 14
Part 2: Placebo	0 of 3 (0%)	1 of 3 (33.3%)	0 of 3
Part 2: GSK2838232 500 mg Tablet Fed	0 of 7 (0%)	0 of 7 (0%)	0 of 7

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 32558338Johnson M, Jewell RC, Gan J, Dumont E, Burns O, Johns BA. A Phase 1 Study to Assess the Relative Bioavailability, Food Effect, and Safety of a Tablet Formulation of GSK2838232, a Novel HIV Maturation Inhibitor in Healthy Participants After Single and Repeated Doses. Clin Pharmacol Drug Dev. 2020 Nov;9(8):972-977. doi: 10.1002/cpdd.820. Epub 2020 Jun 18.
Individual participant dataSharing planned: Yes. IPD for this study is available via the Clinical Study Data Request site.

Related trials for Infection, Human Immunodeficiency Virus

Not yet recruiting
Bwelela Easy Study
HIV, HIV - Human Immunodeficiency Virus
RecruitingPhase 2
Doravirine (DOR) in Human Immunodeficiency Virus (HIV)-Infected Children Aged 4 Weeks to <12 Years and <45 kg (MK-1439-066)
Human Immunodeficiency Virus (HIV) Infection
RecruitingPhase 1
Dasatinib for HIV-1 Reservoir Reduction
HIV Infections
RecruitingObservational study
Leukapheresis to Obtain Plasma or Lymphocytes for Studies of HIV-infected Patients, Including Long-term Non-progressors
HIV
RecruitingObservational study
Evaluation of Patients With HAM/TSP
HTLV-I Infection, Tropical Spastic Paraparesis

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State (time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1 and 2 of Part 1). The study lists 24 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03234036, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2020.